This research is an extension of ongong investigations of the role of the milieu in regulating neuronal growth and development. These studies will examine the biochemical consequences of intercellular interactions, and the role of such interactions in regulating neuronal phenotypic, expression. The rat sympathetic superior cervical ganglion (SCG) in vitro will be used to study mechanisms governing neurotransmitter and transmitter-receptor expression and development, and to identify specific molecules which regulate neuronal choice of neurotransmitter. More specificlly we plan to: a) Further purify and characterize a human brain 50 kDa glycoprotein which fosters cholinergic and substance P expression; b) Examine the regulation of neurotransmitter gene transcription in sympatheetic neurons using specific cDNA probes for somatostatin, tyrosine hydroxylase, and substance P; c) Determine whether the transmitter phenotype and the receptor phenotype of sympathetic neurons are coregulated by environmental factors; d) Define the effects of membrane- membrane contact on transmitter and receptor expression, and characterize a Schwann cell plasma membrane molecule which stimulates cholinergic and substance P development. In a broader sense, these studies seek to define the molecular basis of neurotransmitter mutability and synaptic plasticity. It is hoped that these studies may indicate biochemical loci where therapeutic intervention in disease processes may lead to a return to normal neuronal function.